Expanding the potential of NAI-107 for treating serious ESKAPE pathogens: synergistic combinations against Gram-negatives and bactericidal activity against non-dividing cells

The Journal of Antimicrobial Chemotherapy
Cristina BrunatiStefano Donadio

Abstract

To characterize NAI-107 and related lantibiotics for their in vitro activity against Gram-negative pathogens, alone or in combination with polymyxin, and against non-dividing cells or biofilms of Staphylococcus aureus. NAI-107 was also evaluated for its propensity to select or induce self-resistance in Gram-positive bacteria. We used MIC determinations and chequerboard experiments to establish the antibacterial activity of the examined compounds against target microorganisms. Time-kill assays were used to evaluate killing of exponential and stationary-phase cells. The effects on biofilms (growth inhibition and biofilm eradication) were evaluated using biofilm-coated pegs. The frequency of spontaneous resistant mutants was evaluated by either direct plating or by continuous sub-culturing at 0.5 × MIC levels, followed by population analysis profiles. The results showed that NAI-107 and its brominated variant are highly active against Neisseria gonorrhoeae and some other fastidious Gram-negative pathogens. Furthermore, all compounds strongly synergized with polymyxin against Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa, and showed bactericidal activity. Surprisingly, NAI-107 alone was...Continue Reading

References

Aug 19, 2007·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Srdjan StepanovićFilip Ruzicka
Oct 10, 2007·Antimicrobial Agents and Chemotherapy·Carmela T M MascioJared A Silverman
Jan 16, 2008·FEMS Microbiology Reviews·Waldemar VollmerMiguel A de Pedro
Apr 19, 2008·The Journal of Infectious Diseases·Louis B Rice
Apr 25, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Catherine LiuHenry F Chambers
Dec 24, 2008·Antimicrobial Agents and Chemotherapy·Adam BelleyGregory Moeck
Dec 17, 2009·International Journal of Medical Microbiology : IJMM·Tanja Schneider, Hans-Georg Sahl
Sep 22, 2010·Antimicrobial Agents and Chemotherapy·Jennifer H MoffattJohn D Boyce
Jan 12, 2011·Antimicrobial Agents and Chemotherapy·Daniela JabésStefano Donadio
Apr 12, 2012·Antimicrobial Agents and Chemotherapy·Michael HornseyDavid W Wareham
Feb 16, 2013·The Journal of Antimicrobial Chemotherapy·Martti Vaara
Sep 5, 2013·The Journal of Antibiotics·Mark S ButlerMatthew A Cooper
Jan 16, 2014·Journal of Natural Products·Sonia I MaffioliStefano Donadio
Feb 26, 2014·Antimicrobial Agents and Chemotherapy·Meritxell García-QuintanillaMichael J McConnell
Mar 15, 2014·The Journal of Biological Chemistry·Daniela MünchHans-Georg Sahl
Dec 17, 2014·Antimicrobial Agents and Chemotherapy·Alexander J LepakDavid R Andes
Jan 7, 2015·Nature·Losee L LingKim Lewis
Jan 13, 2015·ACS Chemical Biology·Sonia I MaffioliStefano Donadio
Sep 24, 2015·International Journal of Antimicrobial Agents·Meritxell García-QuintanillaMichael J McConnell
Oct 30, 2015·Journal of Natural Products·João C S CruzStefano Donadio
Oct 31, 2015·Journal of Industrial Microbiology & Biotechnology·Sonia I MaffioliStefano Donadio
Dec 10, 2015·Infectious Diseases and Therapy·Phillip J BergenBrian T Tsuji
Jan 23, 2016·Nature·Eric D Brown, Gerard D Wright
Mar 1, 2016·ACS Infectious Diseases·Helen I ZgurskayaS Gnanakaran
Sep 23, 2016·JAMA : the Journal of the American Medical Association·Hilary D MarstonAnthony S Fauci
Oct 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Anna MüllerLeendert W Hamoen
Nov 21, 2016·International Journal of Antimicrobial Agents·Justin R LenhardBrian T Tsuji
Dec 17, 2016·Science·Alexander HarmsKenn Gerdes

❮ Previous
Next ❯

Citations

Apr 28, 2020·Journal of Clinical Pharmacy and Therapeutics·Taciéli Fagundes da RosaRosmari Hörner
Aug 23, 2019·World Journal of Microbiology & Biotechnology·Vasundhera GuptaSuresh Korpole
Feb 1, 2019·Scientific Reports·Marcel LagedrosteLutz Schmitt
Jan 16, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Martti Vaara
Nov 17, 2020·Frontiers in Microbiology·Jens ReinersLutz Schmitt
Feb 27, 2021·Chemical Society Reviews·Sam M Rowe, David R Spring
Mar 4, 2020·Biochimica Et Biophysica Acta. Biomembranes·Xiaoqi WangEefjan Breukink
May 9, 2021·Applied and Environmental Microbiology·Anton Du Preez van StadenCarine Smith
Oct 15, 2021·Natural Product Reports·Roberto G S BerlinckJairo I Quintana-Bulla

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Biofilm & Infectious Disease

Biofilm formation is a key virulence factor for a wide range of microorganisms that cause chronic infections.Here is the latest research on biofilm and infectious diseases.

Biofilms

Biofilms are adherent bacterial communities embedded in a polymer matrix and can cause persistent human infections that are highly resistant to antibiotics. Discover the latest research on Biofilms here.

Acinetobacter Infections

Acinetobacter infections have become common in hospitalized patients, especially in the intensive care unit setting and are difficult to treat due to their propensity to develop antimicrobial drug resistance. Discover the latest research on Acinetobacter Infections here.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.